Pakistan has the fourth highest number of child deaths in the world with more than 500,000 children dying annually before the age of 5 years. Nearly one quarter of this mortality is due to lower respiratory tract infections (LRTI). The role of respiratory viruses as primary pathogens, or co-pathogens with bacteria in childhood LRTI in Pakistan has not been determined. We hypothesize that respiratory syncytial virus (RSV) and influenza virus play an important role in the etiology of LRTI in children <5 year old in Pakistan. The objective of this proposal is to determine the disease burden due to RSV and influenza virus in children in Pakistan. The specific aims are 1) to advance viral diagnostic capacity in Pakistan 2) to determine the prevalence of RSV and influenza virus in <5 year old children hospitalized with fever or respiratory illness at two tertiary care hospitals in Karachi, Pakistan and 3) To determine the community based incidence of LRTI associated with RSV and influenza virus in <5 year old children at Bilal Colony (an urban slum) in Karachi, Pakistan. Since influenza vaccines are currently available and RSV vaccines are in advanced development, these studies will establish baseline disease rates and present objective assessment of the need for introducing these vaccines in Pakistan. In the first year of the study, Dr. Ali will lead the establishment of viral culture set up at Aga Khan University in Pakistan, with the help of mentors at Vanderbilt University in United States. This will be followed by 2 years of hospital based surveillance and then 2 years of community based active surveillance to find the burden of RSV and influenza virus in <5 year old children in inpatient and outpatient settings in Karachi, Pakistan. If a significant burden is confirmed, then a study to use viral vaccines to reduce this burden can be proposed to other funding agencies. PUBLIC HEALTH RELEVANCE: Pneumonia is the leading cause of child mortality in Pakistan. Role of respiratory syncytial virus and influenza virus in the etiology of childhood pneumonia in Pakistan is not known, and will be the focus of this investigation. If these viruses are found to be significant pathogens, then vaccines against these viruses may reduce the pneumonia associated child mortality in Pakistan.